Comparison of Standard Versus Low Dose Advagraf® With or Without Angiotensin-converting Enzyme Inhibitor (ACEi)/Angiotensin Receptor Blocker (ARB) on Histology and Function of Renal Allografts
- Conditions
- Kidney Transplantation
- Interventions
- Drug: Corticosteroids
- Registration Number
- NCT00933231
- Lead Sponsor
- Astellas Pharma Inc
- Brief Summary
This is a multicentre study examining the use of Advagraf-minimization strategy and/or the use of an inhibitor of the renin-angiotensin system in reducing chronic rejection in renal allografts.
- Detailed Description
The study will consist of the following 4 treatment groups.:
1. Standard dose Advagraf with angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) antihypertensive therapy
2. Standard dose Advagraf without ACEi/ARB antihypertensive therapy
3. Low dose Advagraf with ACEi/ARB antihypertensive therapy
4. Low dose Advagraf without ACEi/ARB antihypertensive therapy
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 281
- Subject is the recipient of a first or second deceased or living donor renal transplant (one kidney only)
- Subject must have at least one HLA-mismatch with the donor. HLA identical donor-recipient pairs are not eligible
- Subject understands either English or French
- If female and of child-bearing potential, subject has a negative pregnancy test and utilizes adequate contraceptive methods
- Presence of donor specific antibody
- Subject who is currently participating in a study with investigational drug, or who has received investigational drug within three months prior to randomization. Observational studies are acceptable
- Subject who has lost a previous graft for immunological reasons less than one year from transplant
- Subject is pregnant or breastfeeding
- Subject receives a kidney lacking pre-implantation biopsy
- Subject has significant disease (e.g. malignancy or uncontrolled infection) or disability (e.g. cognitive defect) which prevents understanding of, or adherence to the protocol
- Subject who in the opinion of the Investigator, require ACEi/ARB therapy post-transplant for any indication
- Subject who requires induction with Thymoglobulin, Campath, antithymocyte globulin (ATG), antilymphocyte globulin (ALG) or any biological induction agent other than basiliximab. Unplanned post-transplant use of these prohibited drugs for clinical indications post-transplant is allowed
- Subject has plans to become pregnant within 2 years post-transplant
- Subject who has a positive T-cell or B-cell crossmatch. Subjects with a weakly positive B-cell cross-match that tests negative following DTT reduction are acceptable
- Subject who has a requirement for maintenance immunosuppressant therapy with the exception of low dose steroid or mycophenolate mofetil (MMF). A subject who is on low dose tacrolimus maintenance therapy will be eligible provided the tacrolimus is withheld at least 1 week prior to transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Tacrolimus Standard Dose without ACEi/ARB Cellcept Participants receive a standard dose of tacrolimus without ACEi/ARB. Tacrolimus Standard Dose without ACEi/ARB Corticosteroids Participants receive a standard dose of tacrolimus without ACEi/ARB. Tacrolimus Standard Dose with ACEi/ARB tacrolimus Participants receive a standard dose of tacrolimus with ACEi/ARB. Tacrolimus Standard Dose with ACEi/ARB Simulect Participants receive a standard dose of tacrolimus with ACEi/ARB. Tacrolimus Standard Dose with ACEi/ARB Cellcept Participants receive a standard dose of tacrolimus with ACEi/ARB. Tacrolimus Standard Dose with ACEi/ARB Corticosteroids Participants receive a standard dose of tacrolimus with ACEi/ARB. Tacrolimus Standard Dose with ACEi/ARB Ramipril Participants receive a standard dose of tacrolimus with ACEi/ARB. Tacrolimus Standard Dose with ACEi/ARB Irbesartan Participants receive a standard dose of tacrolimus with ACEi/ARB. Tacrolimus Standard Dose without ACEi/ARB tacrolimus Participants receive a standard dose of tacrolimus without ACEi/ARB. Tacrolimus Standard Dose without ACEi/ARB Simulect Participants receive a standard dose of tacrolimus without ACEi/ARB. Tacrolimus Low Dose with ACEi/ARB tacrolimus Participants receive a low dose of tacrolimus with ACEi/ARB. Tacrolimus Low Dose with ACEi/ARB Simulect Participants receive a low dose of tacrolimus with ACEi/ARB. Tacrolimus Low Dose with ACEi/ARB Cellcept Participants receive a low dose of tacrolimus with ACEi/ARB. Tacrolimus Low Dose with ACEi/ARB Corticosteroids Participants receive a low dose of tacrolimus with ACEi/ARB. Tacrolimus Low Dose with ACEi/ARB Ramipril Participants receive a low dose of tacrolimus with ACEi/ARB. Tacrolimus Low Dose with ACEi/ARB Irbesartan Participants receive a low dose of tacrolimus with ACEi/ARB. Tacrolimus Low Dose without ACEi/ARB Simulect Participants receive a low dose of tacrolimus without ACEi/ARB. Tacrolimus Low Dose without ACEi/ARB tacrolimus Participants receive a low dose of tacrolimus without ACEi/ARB. Tacrolimus Low Dose without ACEi/ARB Cellcept Participants receive a low dose of tacrolimus without ACEi/ARB. Tacrolimus Low Dose without ACEi/ARB Corticosteroids Participants receive a low dose of tacrolimus without ACEi/ARB.
- Primary Outcome Measures
Name Time Method Percentage of Participants with the Presence of Allograft Interstitial Fibrosis and Tubular Atrophy (IF/TA) as Assessed at a Central Pathology Lab up to 24 months Progression of IF/TA from Month 6 to Month 24 up to 24 months
- Secondary Outcome Measures
Name Time Method Graft Survival up to 5 years Renal Function as Measured by Ratio of Urine Protein and Creatinine Concentrations up to 5 years Time to First Any Acute Rejection up to 24 months Urine Renal Biomarkers up to 24 months 12-Item Short Form (SF-12) Health Survey: Physical Composite Score (PCS) and Mental Health Composite Score (MCS) up to 24 months The PCS and MCS are measured on a normalized 0-100 scale and computed using the corresponding subdomains from the SF-12 with 0 being the lowest level of health and 100 the highest.
Kidney Transplant Recipient Opinions of Immunosuppressive Medications Questionnaire up to 24 months This questionnaire consists of 11 questions regarding immunosuppressive medications, where questions 1-3 ask about your experiences and opinions of transplant anti-rejection medications, questions 4 and 11 ask to rate each medication on the scale of 1-10, with 1 meaning disagree completely and 10 meaning agree completely, and questions 5-10 ask which medication satisfies the question.
Percentage of Participants with Polyomavirus Infection up to 12 months Time to T-cell Banff Mediated Rejection as Assessed at a Central Pathology Lab up to 24 months Banff 2007 Individual Sub-scores up to 24 months Banff 2007 sub-scores (AH = Arteriolar hyalinethickening score; AT = Tubulitis score; AV = Intimal arteritis score; AI = Interstitial inflammation score; AG = Glomerulitis score; CG = Glomerulopathy score; CI = Interstitial fibrosis score; CT = Tubularatrophy score; CV = Vascular fibrous intimal thickening score; MM = Mesangial matrix increase score; TI = Total interstitial inflammation score; PTC = Peritubulary capillaritis score) is measured on an ordinal scale of 0 - 3.
Change from Baseline in Chronic Allograft Damage Index Baseline and 6, 24 months Percentage of Participants in Each Category of Banff 2007 Diagnostic Classification of Renal Allograft Pathology up to 24 months Percentage of Participants with Acute Rejections up to 24 months Renal Function as Measured by Serum Creatinine up to 5 years Percentage of Participants with Humoral Rejections up to 24 months Percentage of Participants with Circulating Anti-Donor Antibody up to 5 years Number of Participants with Cellular Immune Response (ELISPOT) up to 6 months Patient Survival up to 5 years Renal Function as Measured by Glomerular Filtration Rate (GFR) up to 5 years
Trial Locations
- Locations (13)
Site CA133 Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
Site CA54 University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Site CA27 London Health Sciences Centre
🇨🇦London, Ontario, Canada
Site CA238 Hôpital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
Site CA142 St. Paul's Hospital
🇨🇦Saskatoon, Saskatchewan, Canada
Site CA116 Centre Hospitalier Universitaire de Sherbrooke- Hôpital Fleuirmont
🇨🇦Sherbrooke, Quebec, Canada
Site CA114 Capital District Health Authority- QEII Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
Site CA172 Hôpital Notre-Dame du CHUM
🇨🇦Montreal, Quebec, Canada
Site CA144 McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Site CA64 Centre Hospitalier Universitaire de Québec- L'Hôtel-dieu de Québec
🇨🇦Quebec, Canada
Site CA150 St. Joseph's Healthcare
🇨🇦Hamilton, Ontario, Canada
Site CA165 St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Site CA141 Health Sciences Centre
🇨🇦Winnipeg, Manitoba, Canada